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Run‐down of the GABAA response under experimental ischaemia in acutely dissociated CA1 pyramidal neurones of the rat.
Author(s) -
Harata N,
Wu J,
Ishibashi H,
Ono K,
Akaike N
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1997.sp022052
Subject(s) - gabaa receptor , neuroscience , ischemia , chemistry , biophysics , biology , medicine , receptor
1. The effect of experimental ischaemia on the response to gamma‐aminobutyric acid (GABA) was assessed in acutely dissociated CA1 pyramidal neurones of rats, using the patch‐clamp technique. 2. Rapid application of 3 x 10(‐5) M GABA induced a bicuculline‐sensitive inward Cl‐ current (IGABA) at a holding potential (Vh) of ‐44 mV. The peak amplitude of IGABA showed a time‐dependent decrease (run‐down) when it was recorded with the conventional whole‐cell mode without internal ATP. The run‐down was not observed when the intracellular ATP concentration ([ATP]i) was maintained by the nystatin‐perforated recording with an intracellular Na+ concentration ([Na+]i) of 0 mM. 3. When [Na+]i was increased to more than 30 mM, the IGABA run‐down was observed even with the nystatin‐perforated recording. 4. The IGABA run‐down observed at 60 mM [Na+]i with the nystatin method was further enhanced under experimental ischaemia without changes in the reversal potential of IGABA. The enhanced run‐down was suppressed by application of the Na+,K(+)‐ATPase inhibitors, ouabain and SPAI‐1. 5. IGABA run‐down during ischaemia was also accompanied by an outward holding current and a concomitant increase in intracellular free Ca2+ concentration ([Ca2+]i) in 48.5% of the neurones. The outward current was a Ca(2+)‐activated K+ current, which was blocked by 3 x 10(‐7) M charybdotoxin. 6. In the inside‐out mode of the single‐channel analysis, GABA activated three subconductance states with conductances of 33.4, 22.7 and 15.2 pS. Reduction of ATP concentration from 2 to 0 mM on the intracellular side suppressed the channel activities, while an increase in Ca2+ concentration from 0.7 x 10(‐9) to 1.1 x 10(‐6) M had no effect. 7. These results suggest that ischaemia induces the run‐down of the postsynaptic GABA response at the GABAA receptor level, and that this run‐down is triggered by a decrease in [ATP]i.